1,747 research outputs found

    Ruolo di sitemi redoz nell'attivazione intracellulare di farmaci e tossine

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    Lo stato d’ossidoriduzione (“redox buffer”) della cellula è regolato principalmente da due sistemi: Glutatione Reduttasi /Glutaredossina Tioredossina Reduttasi / Tioredossina La tioredossina reduttasi (TrxR) e la glutatione reduttasi (GR) appartengono alla famiglia delle piridin nucleotide-disolfide ossidoreduttasi a cui sono ascritti anche enzimi come la lipoamide deidrogenasi, tripanitione reduttasi e la ione-mercurio reduttasi. Essi sono inoltre dei flavoenzimi, in quanto ciascun monomero di cui si compone l’omodimero che li costituisce, contiene come gruppo prostetico una molecola di FAD. Il sito attivo contiene anche un sito di binding per il NADPH. Durante la catalisi gli equivalenti riducenti sono trasferiti dal NADPH al substrato attraverso una molecola di FAD. Il sistema tioredossinico, quindi, è composto dalla tioredossina (Trx) e dalla tioredossina reduttasi (TrxR) e gioca un ruolo importante nella regolazione dello stato redox della cellula [Holmgren, 1985]. Un substrato classico di tioredossina reduttasi è costituito da tioredossina (Trx). In questo sistema enzimatico, il flusso degli elettroni va dalla molecola di NADPH alla Trx. Tioredossina ridotta è quindi in grado di ridurre il proprio substrato (figura 1). Il sistema TrxR/Trx è largamente distribuito tra i procarioti e gli eucarioti ed è coinvolto in molti processi cellulari quali la sintesi di desossiribonucleotidi [Laurent et al., 1964], il controllo redox di numerosi fattori di trascrizione, protezione contro stress ossidativo [Nakamura et al., 1997], crescita cellulare e cancro.not availabl

    Ensemble Kalman Filter vs Particle Filter in a Physically Based Coupled Model of Surface-Subsurface Flow (Invited)

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    Data assimilation (DA) has recently received growing interest by the hydrological modeling community due to its capability to merge observations into model prediction. Among the many DA methods available, the Ensemble Kalman Filter (EnKF) and the Particle Filter (PF) are suitable alternatives for applications to detailed physically-based hydrological models. For each assimilation period, both methods use a Monte Carlo approach to approximate the state probability distribution (in terms of mean and covariance matrix) by a finite number of independent model trajectories, also called particles or realizations. The two approaches differ in the way the filtering distribution is evaluated. EnKF implements the classical Kalman filter, optimal only for linear dynamics and Gaussian error statistics. Particle filters, instead, use directly the recursive formula of the sequential Bayesian framework and approximate the posterior probability distributions by means of appropriate weights associated to each realization. We use the Sequential Importance Resampling (SIR) technique, which retains only the most probable particles, in practice the trajectories closest in a statistical sense to the observations, and duplicates them when needed. In contrast to EnKF, particle filters make no assumptions on the form of the prior distribution of the model state, and convergence to the true state is ensured for large enough ensemble size. In this study EnKF and PF have been implemented in a physically based catchment simulator that couples a three-dimensional finite element Richards equation solver with a finite difference diffusion wave approximation based on a digital elevation data for surface water dynamics. We report on the retrieval performance of the two schemes using a three-dimensional tilted v-catchment synthetic test case in which multi-source observations are assimilated (pressure head, soil moisture, and streamflow data). The comparison between the results of the two approaches allows to discuss some of the strengths and weaknesses, both physical and numerical, of EnKF and PF and to learn the implications related to the choice of the statistics used to build the ensemble of realizations

    Ensemble Kalman filter versus particle filter for a physically-based coupled surface–subsurface model

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    The ensemble Kalman filter (EnKF) and sequential importance resampling (SIR) are two Monte Carlo-based sequential data assimilation (DA) methods developed to solve the filtering problem in nonlinear systems. Both methods present drawbacks when applied to physically-based nonlinear models: the EnKF update is affected by the inherent Gaussian approximation, while SIR may require a large number of Monte Carlo realizations to ensure consistent updates. In this work we implemented EnKF and SIR into a physically-based coupled surface-subsurface flow model and applied it to a synthetic test case that considers a uniform soil v-shaped catchment subject to rainfall and evaporation events. After a sensitivity analysis on the number of Monte Carlo realizations and the correlation time of the atmospheric forcing, the comparison between the two filters is done on the basis of different simulation scenarios varying observations (outlet streamflow and/or pressure head), assimilation frequency, and type of bias (atmospheric forcing or initial conditions). The results demonstrate that both EnKF and SIR are suitable DA methods for detailed physically-based hydrological modeling using the same, relatively small, ensemble size. We highlight that the Gaussian approximation in the EnKF updates leads to a state estimation that can be not consistent with the physics of the model, resulting in a slowdown of the numerical solver. SIR instead duplicates physically consistent realizations, but can display difficulties in updates when the realizations are far from the true state. We propose and test a modification of the SIR algorithm to overcome this issue and preserve assimilation efficiency

    Classification Rules Explain Machine Learning

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    We introduce a general model for explainable Artificial Intelligence that identifies an explanation of a Machine Learning method by classification rules. We define a notion of distance between two Machine Learning methods, and provide a method that computes a set of classification rules that, in turn, approximates another black box method to a given extent. We further build upon this method an anytime algorithm that returns the best approximation it can compute within a given interval of time. This anytime method returns the minimum and maximum difference in terms of approximation provided by the algorithm and uses it to determine whether the obtained approximation is acceptable. We then illustrate the results of a few experiments on three different datasets that show certain properties of the approximations that should be considered while modelling such systems. On top of this, we design a methodology for constructing approximations for ML, that we compare to the no-methods approach typically used in current studies on the explainable artificial intelligence topic

    Extraction of Defeasible Proofs as Explanations

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    Houdini is a Defeasible Deontic Logic reasoner that has been recently developed in Java. The algorithm employed in Houdini follows the proof conditions of the logic to conclude propositional and deontic literals, and is an efficient solution that provides the full extension of a theory. This computation is made in a forward-chaining complete way. Effectiveness is a fundamental property of the adopted approach, but we are also interested in providing an explicit reference to the reasoning that is employed to reach a conclusion. This reasoning is a proof that corresponds to an explanation for that conclusion, and such a proof is less natural to identify in a non-monotonic framework like Defeasible Logic than it would be in a classical one. Depending on the formalism and on the algorithm, the process of reconstructing a proof from a derived conclusion can be cumbersome. Intuitively, a proof consists of a support argument in favour of a literal to be concluded. However, it is necessary also to show that this argument is strong enough, either because the are no arguments against it, or because those arguments are weaker than it. In this paper, with a slight modification of the algorithm of Houdini, we show that it is possible to extract a proof for a defeasible literal in polynomial time, and that such a proof results minimal in its depth

    Text Analytics Can Predict Contract Fairness, Transparency and Applicability

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    There is a growing attention, in the research communities of political economics, onto the potential of text analytics in classifying documents with economic content. This interest extends the data analytics approach that has been the traditional base for economic theory with scientific perspective. To devise a general method for prediction applicability, we identify some phases of a methodology and perform tests on a large well-structured repository of resource contracts containing documents related to resources. The majority of these contracts involve mining resources. In this paper we prove that, by the usage of text analytics measures, we can cluster these documents on three indicators: fairness of the contract content, transparency of the document themselves, and applicability of the clauses of the contract intended to guarantee execution on an international basis. We achieve these results, consistent with a gold-standard test obtained with human experts, using text similarity b ased on the basic notions of bag of words, the index tf-idf, and three distinct cut-off measures

    Improving Groundwater Modeling by Coupled HydroGeophysical Data Assimilation

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    A sequential Bayesian approach for joint assimilation of hydrological and geophysical data in a variably saturated flow model is presented. The study aims to improve simulation results and system understanding by assimilation of multiple type data using a Monte Carlo approach and avoiding the inversion of the geophysical measurements. A SIR based particle filter data assimilation is implemented in a 3D variably saturated flow model. Point measurements are directly assimilated in time while spatial information are blended in the simulation by assimilating Electrical Resistivity Tomography (ERT) measurements. To avoid the inversion of the latter, a forward 3D model of electrical current distribution is implemented as the measurements model in the data assimilation algorithm. The connection with the hydrological parameters occurs via the Archie's law. A synthetic test case is used to test the assimilation of pressure data, ERT data and the joint assimilation of pressure and ERT data. Performance of the proposed modelling approach are evaluated in terms of predicton efficiency and parameter estimation. Perspectives and limitations of coupled hydrogeophysical data assimilation are discussed

    Recycling of Waste Materials Using Bitumen Emulsion for Road Pavement Stabilized Base Courses: a Laboratory Investigation

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    The valorisation and reuse of waste materials can enhance the environmental sustainability of road constructions, especially by means of cold recycling techniques, which, moreover, allow to reduce polluting emissions in atmosphere. Among the various technological approaches, the use of bitumen emulsion to stabilize waste materials is very common, especially in case of reclaimed asphalt pavement (RAP) aggregates. However, even other types of waste materials could be considered using a Cold Central Plant Recycling (CCPR) approach. The paper discusses the main results of a laboratory investigation aimed to evaluate the mechanical performance of bitumen emulsion stabilized mixtures for road pavements base courses, prepared with RAP, steel slag, coal ash and glass wastes, used with various percentages. In a first step of the laboratory study, both physical and toxicological properties of each waste material have been investigated, in order to assess their environmental compatibility. Subsequently, an extensive mechanical analysis of the bitumen emulsion stabilized mixtures has been carried out in the laboratory, in terms of indirect tensile strength, indirect tensile stiffness modulus at three temperatures (10°C, 25°C, 40°C) and repeated load axial tests at 30°C. The moisture resistance of the mixes has been also investigated by means of indirect tensile strength tests carried out on soaked specimens. Very good results have been observed, depending on the mix composition: indirect tensile strength at 25 °C on dry specimens up to 0.52 MPa and stiffness modulus up to 4,056 MPa (at 25 °C, for a rise time equal to 124 ms). Therefore, it has been verified that the waste materials considered in the study can be successfully reused to completely substitute conventional aggregates in bitumen emulsion stabilized mixtures for road pavements base courses

    TUTELA DEL LAVORO E LIBERTA' D'IMPRESA NEI PROCESSI DI ESTERNALIZZAZIONE

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    L’elaborato analizza le conseguenze lavoristiche della successione fra imprenditori, muovendo da una ricognizione delle varie tipologie di esternalizzazione con le relative esigenze e principali criticità. L’indagine si concentra in primo luogo sul trasferimento d’azienda, esaminando la normativa e la giurisprudenza europee per passare poi alla disciplina di diritto interno, alle procedure sindacali e a uno specifico focus sul trasferimento delle aziende in crisi. Successivamente l’autore si sofferma sull’appalto, prendendone in particolare considerazione gli indici di genuinità, i criteri di distinzione dalla somministrazione illecita di manodopera e la tutela delle maestranze in caso di avvicendamento fra imprese. Da ultimo, la ricerca approfondisce le c.d. “clausole sociali”, sia di prima che di seconda generazione, valutandone la compatibilità con il diritto eurounitario e con la costituzione nonché riflettendo sui possibili rimedi in caso di loro violazione.The author analyzes the labour consequences of the succession between entrepreneurs, starting from a recognition of the various types of outsourcing with the related needs and main critical issues. The survey focuses primarily on the transfer of businesses, examining European legislation and case-law and then moving on to internal legislation, trade union procedures and a specific focus on the transfer of companies in crisis. The author then dwells on the contract, taking into account in particular the indications of authenticity, the criteria of distinction from the illicit administration of labour and the protection of workers in the event of turnover between companies. Finally, the research deepens the "social clauses", both first and second generation, assessing their compatibility with European law and with the constitution and reflecting on possible remedies in case of their violation

    Experimental tests on a hybrid timber-frame wall system

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    This paper presents an innovative lateral load-resisting wall system, which is an evolution of the light-timber frame (LTF) shear walls currently available on the market. In comparison to traditional LTF walls, the novelty aspect is the use of Cross-Laminated Timber (CLT) beams and studs instead of solid timber elements. Thanks to this ‘hybrid’ approach, this new system combines some peculiar aspects of LTF structures (such as the limited weight and the high dissipative behaviour) with the potentials of CLT. Moreover, the use of CLT elements limits the issues due to the compressive deformations on bottom beams and permits to employ some innovative connections with high mechanical properties. Cyclic shear tests are carried out on two configurations of interest, assembled by considering different layouts of the load-bearing elements. Test results are compared to the experimental data obtained on similar LTF systems and differences are critically discussed
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